1. Field of the Invention
The present invention relates to microfluidic systems and, more specifically, to a microfluidic system used in atomic force microscopy.
2. Description of the Related Art
Atomic force microscope (AFM) is used by researchers to image surfaces with nanometer lateral resolution and sub-nanometer height resolution. In addition, high resolution imaging can be performed in physiological environments, which include liquids and physiological buffers. Imaging in an enclosed physiological environment is typically accomplished with a “liquid cell,” which can be built in house or obtained commercially. A liquid cell secures the probe of an atomic force microscope and positions the microcantilever tip at the surface to be imaged while maintaining an enclosed and sealed environment containing a small volume of liquid, which can typically be pumped or heated.
However, current systems place the liquids to be imaged in relatively large volumes, thereby making specific molecules difficult to find with the probe. Commercially available liquid cells enclose a volume of liquid using an O-ring gasket that measures approximately one centimeter in diameter or larger and typically enclose a volume of 50 microliters to several milliliters.
For many applications of the AFM, this relatively large volume of liquid is a major drawback. This is because many proteins and other biomaterials are difficult to obtain in large quantities and prolonged imaging assays can only be conducted at very low concentrations of material. As a result, the study of the dynamics of crystal growth by proteins during biomineralization processes is limited by the capability of today's AFM liquid cells. Also current liquid cell designs contain significant “dead volume” in which a reagent pumped to the sample does not distribute uniformly as a consequence of expanding flow lines from the inlet via through the flow cell. A more well-defined flow field would allow a clear interpretation of real-time in situ AFM measurements of kinetic processes.
Typical cells used in AFM imaging include transparent materials to allow the monitoring of cantilever deflection optically and are able to hold the cantilever probe die firmly in place. They also enclose the cantilever in a liquid-tight seal and allow the cantilever tip access to the surface of a sample during imaging or force spectroscopy. Many liquid cells are machined from quartz or plastic with a metal spring that holds the cantilever die in place. A recessed O-ring seals against the sample surface and defines the liquid microenvironment.
Shrinking the flow channel is stymied by the need to enclose both the cantilever, which is microscopic, and the substrate die, which is macroscopic having lengths in millimeters on two dimensions. Many existing liquid cell designs have a macroscopic gasket, which surrounds the entire probe including the cantilever and substrate die.
Therefore, there is a need for a microfluidic cell for use in AFM that maintains a micro-scale volume of liquid near the sensing probe.